Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1 930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NF-κB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NF-κB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.

Nonalcoholic steatohepatitis （NASH） is a chronic liver disease with the main pathological features of hepatic steatosis， inflammatory cell infiltration， and interstitial fibroplasia， and it is an important risk factor for liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. NOD-like receptor protein 3 （NLRP3） inflammasome is the core of innate immunity， and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH， which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine （TCM） and TCM compound prescriptions can improve oxidative stress， regulate lipid metabolism， and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect， while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome， in order to provide ideas for the clinical TCM treatment of NASH， as well as reference targets and research directions for the research and development of new TCM drugs.

Periodontal homeostasis is regulated by the complex interplay between the gingival epithelial barrier, the extracellular matrix of soft tissues, the bone coupling system, and immune responses within the periodontal region. Gingival epithelial cells are primarily composed of keratinocytes and a small proportion of non-keratinocytes, and they are integral to the formation of the gingival epithelial barrier. This epithelial barrier plays a fundamental role in defending against pathogens, exogenous substances, and mechanical stress. This study aims to explore the intrinsic connections between gingival epithelial cells and periodontal homeostasis. Research has shown that gingival epithelial cells participate in maintaining periodontal homeostasis through multiple pathways: ① gingival epithelial cells respond to the inflammatory environment by undergoing proliferation, migration, epithelial-mesenchymal transition, and forming apoptosis-mediated neutrophil extracellular traps; ② when gingival inflammation damages the epithelial barrier, lipopolysaccharides cannot be easily removed, and gingival epithelial cells play a defensive role by activating innate immune responses; ③ the interactions of gingival epithelial cells with oral microbiota and immune cells are essential for maintaining periodontal homeostasis. Thus, gingival epithelial cells are closely associated with periodontal homeostasis. However, the crucial role and mechanisms of gingival epithelial cells in the maintenance of periodontal homeostasis are not clear, which provides novel insights for the research of periodontal homeostatic medicine.

Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1 930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NF-κB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NF-κB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.

Objective:To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.Methods:The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group ( n=54) and the survival group ( n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately. Results:Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups ( P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups ( P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L ( P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05). Conclusions:There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.

Congenital hypothyroidism is one of the common endocrine disorders in newborns，which is mainly caused by thyroid dysgenesis or dyshormonogenesis.DUOX2 gene mutation is a common pathogenic gene of thyroid hormone production disorder，which mainly affects production the hydrogen peroxide needed for thyroid hormone synthesis.In recent years，there are some reports shown that differences in population and regional distribution of DUOX2 gene mutations，and the relationship between different types of mutations and clinical phenotypes is unclear.Compound heterozygous or homozygous mutations can cause severe inactivation of DUOX2 protein，but the clinical phenotypes may be transient CH.Although CH is considered to be a monogenic disorder，some cases have monoheterozygous disease or oligogenic coexistence，and the correlation between oligogenic coexistence to the clinical phenotypes is uncertain.This article provides a review for the structure and function of DUOX2 gene，the characteristics of population distribution and recent advances in the relationship between DUOX2 gene mutations and clinical phenotypes with CH.

Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.

Objective:To summarize the genetic etiology, clinical characteristics and outcomes of neonatal hypotonia in the early stage of NICU, to provide basis for clinicians to early identify diseases and choose reasonable treatments.Methods:The clinical data of neonates with hypotonia admitted to the Department of Neonatology of Children′s Hospital of Xinjiang Uygur Autonomous Region and People′s Hospital of Xinjiang Uygur Autonomous Region from July 2017 to July 2020 were analyzed.Results:A total of 49 children were enrolled in the study, all clinically manifested as unexplained hypotonia, accompanied by special appearance 29 cases(59.18%), metabolic abnormality 18 cases(36.73%), and cranial imagin abnormality 23 cases(46.93%). After gene sequencing a, total of 22(44.89%)patients were confirmed.Thirteen (26.53%) of them were copy number variation, and gene mutation in nine cases(18.36%). The oldest age of these patients was 3 years and 2 months now, while the youngest was 4 months.A total of 16 patients were dead(32.65%). Four (8.16%) patients were lost to follow-up.At present, eighteen (62.07%) patients had mental retardation, and eleven (37.93%) of whom still existed severe physical retardation.Conclusion:We could conduct genetic testing in NICU to improve the diagnosis rate of neonates with unexplained hypotonia, which have high rate of adverse events.Neonates with a clear diagnosis should be treated promptly and give the genetic counseling to reduce the risk for the next children.

【Objective】 To investigate the frequencies of HLA-B alleles in Jiangsu Han population from Chinese Marrow Donor Program (CMDP) Jiangsu Branch in 8 prefecture-level cities, compare and analyze the distribution of common susceptible alleles at HLA-B locus in 8 prefecture-level cities. 【Methods】 The HLA-B locus of 27 249 unrelated volunteers from CMDP Jiangsu Branch were genotyped by polymerase chain reaction–sequence based typing (PCR-SBT) method, and frequencies of HLA-B alleles of 8 prefecture-level cities were calculated and compared. 【Results】 A total of 145 HLA-B alleles were detected in Jiangsu Han population, among them 104, 113, 83, 88, 88, 85, 84, 72 HLA-B alleles were detected in Changzhou, Nanjing, Zhenjiang, Yangzhou, Huai’an, Suqian, Xuzhou, and Yancheng Han population, respectively. In general, the common alleles in Changzhou, Yangzhou and Zhenjiang were very similar, and the most common alleles were B^*46∶01, 13∶02, 40∶01 and 58∶01. The common alleles in Nanjing, Huai’an and Suqian were rather similar, and the most common alleles were B^*13∶02, 46∶01, 40∶01, 58∶01 and 51∶01. The common alleles in Yancheng were rather similar to Nanjing, Huai’an and Suqian, with only difference in the order of B^*40∶01 and B^*58∶01. The common alleles in Xuzhou were close to Nanjing, Huai’an and Suqian too, with only difference in the order of B^*40∶01 and B^*46∶01. 【Conclusion】 The results reflected the distribution of HLA-B alleles of Jiangsu Han population from 8 prefecture-level cities and the gene distribution was basically consistent with the regional distribution. The major difference in HLA-B locus in Jiangsu 8 prefecture-level cities was B ^* 13∶02 and B ^* 46∶01. The frequency of B ^* 13∶02 in Northern Jiangsu (Huai’an, Suqian, Xuzhou, Yancheng) is much higher than that of B ^* 46∶01, and that in Nanjing is slightly higher than the frequency of B ^* 46∶01, which is consistent with that in North China. The frequency of B ^* 46∶01 in Southern Jiangsu (Changzhou), Yangzhou and Zhenjiang is higher than that of B ^* 13∶02, which is consistent with that in South China. The polymorphism analysis of alleles at HLA-B locus in 8 cities in Jiangsu Province provided significant basic data for the study of the correlation between HLA-B locus genes and diseases, as well as the population genetics and anthropology in Jiangsu Han population.